1. Field of the Invention
The invention relates to a hydrogel, and more particularly to a biodegradable copolymer hydrogel.
2. Description of the Related Art
In most instances, a substitutive tissue must be used to recover the functionality of body tissue damaged by disease, unless the original tissues have a high inherent regeneration capacity. The unavailability of acceptable human donor organs, and the low rate of long term success due to host versus graft rejection are the main challenges now facing the field of tissue and organ transplantation.
In order to solve the above problems, biomaterials (such as synthetic or natural matrix serving as carriers) are provided to be implanted in the desired region to facilitate cell seeding. According to medical statistics, approximately 30% of tissue reconstruction processes performed relate to bone tissue reconstruction.
In recent years, biomaterials have been applied to reconstruct hard tissues and soft tissues of bone structures. For reconstruction of hard tissues, a key challenge is to facilitate fixation of bone fragments in an articular surface fracture or a comminuted fracture. Thus, a bone fixation device has been developed. The bone fixation device, such as a K-pin, bone nail, or cable or anchor, had a micro-textured contact surface to enhance the installation or gripping characteristics thereof.
For soft tissues, adherence to the bone fragments are peeled off before using bone fixation devices, thereby causing poor circulation of blood and increasing risk of nonunion fracture. In addition, when using bone fixation devices for soft tissues, bone fragments are further disintegrated following the surgical operation.
At present, most bone cements are primarily made of polymethyl methacrylate (PMMA). The bone cement can provide sufficient strength for the bone fracture at an early stage. Patients using the bone cement are not apt to develop allergies thereto due to the biologically inert properties thereof. Specifically, the bone cement is non-biodegradable. Therefore, the fixation of bone fragments using the bone cement is not a substantially complete bone union and the bone cement is not suitable for traumatic fractures.
For soft tissues repair, sutureless anchors and knotless anchors are used to substitute suture anchors in order to avoid histological reactions resulting from knots and reduce the surgical time. The sutureless anchor, however, is apt to cause ridgy regenerative tissues due to stress, resulting in the ridgy regenerative tissues and the original tissues not being able to dovetail into each other. A bioadhesion can be further used to increase the anastomosis between the original tissues and the regenerative tissues fixed by the knotless anchors or sutureless anchors, enhancing the regeneration of tissues.
Further, bioadhesion can be applied in the ischemic necrosis of femoral head repair, such as the reconstruction of a hip joint. Avascular necrosis (AVN) is a disease, for young adults, resulting from the temporary or permanent loss of blood supply to bones. With early diagnosis, at least 75% of the patient with AVN can recover after treatment. Various treatments for AVN focus on salvaging the head of the femur or other bone or joint such as core decompression. A necrotic tissue is first removed and packed with an autologous cancellous bone leaving room for the insertion of an autologous fibular graft with an autologous fibular graft vascular pedicle, the peroneal vessels, attached, to provide abundant blood flow to the head of a femur. An anastomosis is performed between the lateral circumflex vessels and the fibula vascular pedicle. Although the procedure is oftentimes successful in stabilizing the femoral head and providing blood flow to the femoral head, it carries the risk for donor sight morbidity. A bioadhesion can be used, combined with a drug and implanted into the femoral head. With the degradation of bioadhesion, the drug is gradually released, facilitating the regeneration of bones and veins.
Further, bioactive substance (e.g. drugs, growth factors, nucleic acids etc.) delivery is very important in the biomedical applications comprising tissue engineering, cell therapy and disease medical therapy. The materials for the delivery carriers must provide biocompatible and biodegradable properties for feasible implantation. Preferably, the material is a fluid ex vivo for easy mixing with drugs and transformation into a gel after being injected into the body by a syringe, catheter or laparoscope for delivering the bioactive substances to the desired tissue area. After, the drugs are released over time, achieving a therapeutic effect.
U.S. Pat. No. 5,514,380 discloses a biodegradable copolymer gel with controllable release profiles. The biodegradable copolymer gel, which is a multi-block copolymer, comprises hydrophilic polymer chains such as polyethyleneoxide (PEO) and hydrophobic polymer chains such as polylactic acid (PLA), polyglycolide acid (PGA), polylactide-glycolide (PLGA), or polycaprolactone (PCL). However, the patent makes no mention of temperature sensitivity of the biodegradable copolymer gel.
U.S. Pat. No. 5,702,717, U.S. Pat. No. 6,004,573, U.S. Pat. No. 6,117,949 and U.S. Pat. No. 6,117,949 disclose a temperature sensitive tri-block biodegradable copolymer, represented by ABA or BAB, wherein A is polyester and B is polyethylene glycol, with a average molecular weight of 2000-4990 g/mole. Due to the reverse thermal gelation properties of the biodegradable copolymer, when an aqueous composition including the biodegradable copolymer and a drug is heated (for example: when injected into a human body) over its gelation temperature, its viscosity increases and it transforms into a gel. Therefore, the drug release rate can be controlled by the in vivo hydrolysis rate of the gel. Further, the hydrolysate of the biodegradable copolymer has no cytotoxicity. However, the biodegradable copolymers have a lower critical solution temperature (LCST) of more than 37° C., and the patents do not provide examples proving that the biodegradable copolymers can serve as drug release rate controlling materials.
U.S. Pat. No. 6,136,333 discloses a block copolymer represented by AB or ABA, wherein A is polyester, and B is polyoxyalkylene. The AB di-block copolymer had an EO/LA ratio of between 0.1-100, wherein the cross-linking agent is hexamethylene diisocyanate (HMDI). The block copolymer can serve as anti-adhesion materials, but the patent makes no mention of temperature sensitivity of the block copolymer.
Currently, few delivery materials satisfy all requirements for body compatibility. For gels formed via chemical reactions, the activity of bioactive substances may be influenced to damage the implanted tissue. For materials that possess temperature-sensitivity and gelling property, they also possess poor biodegradability, so that they are not satisfactorily implanted inside of patients. There is, therefore, still a need for a low temperature sensitive and biodegradable copolymer that has no cytotoxicity after degradation.